GAP-JUNCTION-MEDIATED PROPAGATION AND AMPLIFICATION OF CELL INJURY

Gap junctions are conductive channels that connect the interiors of co upled cells. We determined whether gap junctions propagate transcellul ar signals during metabolic stress and whether such signaling exacerba tes cell injury. Although overexpression of the human proto-oncogene b cl2 in C6 glioma cells normally increased their resistance to injury, the relative resistance of bcl2(+) cells to calcium overload, oxidativ e stress and metabolic inhibition was compromised when they formed gap junctions with more vulnerable cells. The likelihood of death was in direct proportion to the number and density of gap junctions with thei r less resistant neighbors. Thus, dying glia killed neighboring cells that would otherwise have escaped injury. This process of glial 'fratr icide' may provide a basis for the secondary propagation of brain inju ry in cerebral ischemia.